Urinary selective serotonin reuptake inhibitors across critical windows of pregnancy establishment: a prospective cohort study of fecundability and pregnancy loss

Fertil Steril. 2020 Dec;114(6):1278-1287. doi: 10.1016/j.fertnstert.2020.06.037. Epub 2020 Oct 14.

Abstract

Objective: To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss.

Design: Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive.

Setting: Four clinical sites.

Patient(s): A total of 1,228 women without uncontrolled depression/anxiety, attempting natural conception while participating in a randomized trial of preconception-initiated low-dose aspirin.

Interventions(s): Not applicable.

Main outcome measure(s): Urinary SSRIs (fluoxetine, sertraline, escitalopram/citalopram) were measured while trying to conceive and, for women who became pregnant, at weeks 0, 4, and 8 of pregnancy. Fecundability odds ratios and incidence of pregnancy loss and live birth were estimated.

Result(s): A total of 172 women (14%) were exposed to SSRIs while trying to conceive. SSRI exposure was associated with 24% reduced fecundability, and accordingly, a nonsignificant 9% lower live birth incidence, with significantly lower live birth in fluoxetine-exposed women. SSRI exposure was not associated with subsequent pregnancy loss, whether exposure was before conception or at 0, 4, or 8 weeks of gestation, although estimates varied by specific SSRI drug.

Conclusion(s): Women using SSRIs may have more difficulty becoming pregnant, and although SSRI exposure overall was not associated with pregnancy loss, fluoxetine deserves caution and future study.

Clinical trial registration number: NCT00467363.

Keywords: Fecundability; SSRI; antidepressant; miscarriage; selective serotonin reuptake inhibitors.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Abortion, Spontaneous / chemically induced*
  • Abortion, Spontaneous / diagnosis
  • Abortion, Spontaneous / urine
  • Adult
  • Citalopram / urine
  • Female
  • Fertility / drug effects*
  • Fluoxetine / adverse effects
  • Fluoxetine / urine
  • Humans
  • Live Birth
  • Pregnancy
  • Pregnancy Trimester, First / urine
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / urine*
  • Sertraline / adverse effects
  • Sertraline / urine
  • Time Factors
  • United States
  • Young Adult

Substances

  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Citalopram
  • Sertraline

Associated data

  • ClinicalTrials.gov/NCT00467363